The objective of this research is to further our understanding of the cellular and molecular mechanisms participating in human IgE antibody responses. The events involved in human IgE production and homeostasis will be dissected through the application and extension of in vitro systems for antibody and IgE biosynthesis, hybridoma antibodies, and controlled in vivo antigen exposure. Spontaneous IgE secreting and pokeweed mitogen response B cell frequencies will be determined by limiting dilution analysis and the surface Ig phenotype of these populations determined through isotype enrichment and depletion. Other B cell subpopulations possibly involved in IgE production will be explored through in vitro stimulation with Ebstein-Barr virus, PPD, and antigens. After immunization the in vitro kinetics of appearance of functional B cell subpopulations for specific IgE antibody will be examined. We will use antigens known to define the responder atopic population (grass antigens) as well as antigens which define a different responder group (hymenoptera venoms) and antigens which do not have a high responder population (tetanus toxoid). These investigations into the effector B cells involved in IgE synthesis will further delineate their roles in normal IgE production and the differences occurring in excessive IgE production states. The other phase of this research is to examine the regulatory and accessory cells involved in modulating IgE responses. We will assess the in vivo events which effect the presence of a subpopulation of normal IgE suppressor T cells lacking in association with hyperimmunoglobulinemia E. T suppressor cells for IgE antigen specific responses will be examined in relation to immunization as well as in vitro antigen exposure. We will assess the role of suppressor cells which contain a membrane receptor for adenosine as these cells can inhibit IgG but not IgM antibody responses in vitro. We will evaluate in vitro the possible in vivo production of auto-antibodies in atopy which may be directed against IgE regulatory cells and result in a high IgE responder state as such auto-antibodies may provide the link between allergy, autoimmunity and immune deficiency. Antigen presentation by adherent monocyte/macrophage cells will be examined utilizing an in vitro monocyte dependent antibody producing system with appropriate normal/patient cross-overs.